Role and possible mechanism of estrogen receptor α down-regulation leading to damage of TM4 Sertoli cell connectivity in mice / 中国药理学通报

Aim To investigate the role of autophagy in the dysfunction of testicular TM4 cell junction induced by ERα down-regulation. Methods TM4 cells were treated with different concentrations of E R a inhibitor ICI182780 (ICI), and the proliferative activity of TM4 cells was detected by CCK-8 method. The number and morphological changes of TM4 cells were observed by light microscope. The levels of E R a, junction function related proteins and autophagy marker proteins were detected by Western blot. The expression and localization of Cx43 were detected by immunofluorescence staining. The cells were treated with chloroquine (CQ) and ICI for 24 h. The expression levels of autophagy and junction function related proteins were detected by Western blot. Results When ICI concentration was 50 nmol • L ~ or above, the cell viability decreased significantly. The increase of cell vacuoles in ICI group was observed by light microscope. Compared with normal control group, the protein expression levels of E R a, ZO-1, occludin, claudin-11, p-catenin and Cx43 in ICI groups significantly dropped, while the expression levels of N-cadherin and E-cadherin had no significant changes; LC3 II significantly rose, while p62 expression significantly fell. The results of immunofluorescence showed that the fluorescence expression of Cx43 in ICI group decreased significantly, but the position of CX43 did not change significantly. Compared with ICI group, the expression levels of LC3 II, p62, Cx43, ZO-1 and β-Catenin significantly increased. Conclusions The down-regulation of E R a leads to damage of TM4 cell junction function, which may be related to the activation of autophagy.

Exploration on Effect of Yinhuotang on Depression-like Behavior in Mice with Bilateral Ovariectomy Induced by Chronic Stress Based on E2/ERβ Signaling Pathway / 中国实验方剂学杂志

Objective:To observe the effect of Yinhuotang （YHT） on the depression-like behavior of mice with bilateral ovariectomy （OVX） induced by chronic stress and explore its action mechanism based on estradiol （E₂）-estrogen receptor <italic>β </italic>（ER<italic>β</italic>） pathway. Method:The experiment was divided into two parts. In the first part， mice were randomly divided into the sham operation （Sham） group， model （OVX） group， positive drug （E₂， 0.13 mg·kg^-1） group， and YHT （23.4 g·kg^-1） group. The OVX model was reproduced by OVX combined with chronic unpredictable mild stress （CUMS）. On the 8th day after OVX， the mice in each group were exposed to CUMS and treated with drugs. The changes in immobility time， horizontal movement score， and vertical movement score of mice in each group were observed in forced swimming test （FST）， tail suspension test （TST） and open-field test （OFT）， respectively. Serum and brain E₂ levels were detected by enzyme-linked immunosorbent assay （ELISA）， the aromatizing enzyme （Cyp19） mRNA expression by real-time fluorescence polymerase chain reaction （Real-time PCR）， the expression of ER<italic>α</italic> and ER<italic>β</italic> in dentate gyrus of hippocampus by immunohistochemistry （IHC）， and the total ER<italic>α</italic> and ER<italic>β</italic> levels in the brain by Western blotting. In the second part， the mice were divided into the Sham group， OVX group， YHT group， and blocker （Y+B， 23.4 g·kg^-1+100 μg·kg^-1） group. Mice in the Y+B group were first treated with intragastric administration of YHT and then with intraperitoneal injection of ER<italic>β</italic> blocker （PHTPP） on the next day. The changes in immobility time， horizontal motor score， and vertical motor score were observed in the three behavioral tests. Result:Compared with the Sham group， the OVX group displayed significantly increased immobility time， decreased horizontal and vertical movement scores （<italic>P</italic><0.01）， down-regulated serum and brain E₂levels （<italic>P</italic><0.01） and Cyp19 mRNA expression in the brain （<italic>P</italic><0.01）， and up-regulated total ER<italic>β</italic> in dentate gyrus and brain （<italic>P</italic><0.01）. However， there was no significant change in total ER<italic>α</italic> expression in the dentate gyrus or brain. As revealed by comparison with the OVX group， the immobility time of the E₂ group was decreased significantly， while the horizontal and vertical movement scores were increased significantly （<italic>P</italic><0.01）. The E₂ levels in the serum was significantly elevated （<italic>P</italic><0.01）. The Cyp19 mRNA expression in the brain and the total ER<italic>α</italic> expression in the dentate gyrus and brain were not significantly changed， while the expression levels of total ER<italic>β</italic> in dentate gyrus and brain were significantly increased （<italic>P</italic><0.01）. In the YHT group， the immobility time declined significantly， and the horizontal and vertical movement scores rose significantly （<italic>P</italic><0.01）. The serum E₂ did not increase， whereas the brain E₂ increased significantly （<italic>P</italic><0.01）. The expression of Cyp19 gene in the brain was significantly increased （<italic>P</italic><0.05，<italic>P</italic><0.01）. There was no significant change in the total ER<italic>α</italic> of dentate gyrus and brain， but the expression levels of total ER<italic>β</italic> in dentate gyrus and brain were significantly increased （<italic>P</italic><0.05，<italic>P</italic><0.01）. PHTPP reversed the effects of YHT on OVX mice in FST， TST and OFT. Conclusion:YHT promotes the synthesis and release of endogenous estrogen in brain and improves the depression-like behavior of OVX mice induced by chronic stress， which is possibly related to the activation of E₂/ER<italic>β</italic> pathway.

Changes in expression of estrogen receptor α and β associated with anxiety-like behavior of dams in dams-offspring separation of C57BL/6 J mice / 解剖学报

Objective To investigate the effects of dams-offspring separation on anxiety-like behaviors of dams, and if these anxiety-like behaviors of dams are associated with estrogen receptorα(ERα) and β( ERβ)in some brain regions. Methods Thirty C57BL/6 J female mice were divided into three groups, control group (CG, n= 10,non-isolated group), short-term separation group( SG,/i= 10, dams were separated from their offspring for 15 minuts per day from the second day to the tenth day after childbirth ) and long-term separation group ( LG, n = 10, dams were separated from their offspring for 3 hours per day from the second day to the tenth day after childbirth ). Anxiety-like behaviors of dams were evaluated in an open-field (OF) and elevated plus-maze test ( EPM ). The level of ERα- immunoreactive neurons (ERα-IRs) and ERβ-immunoreactive neurons (ERβ-IRs) in three brain regions including medial preoptic area (mPOA), hypothalamic ventromedial nucleus (VMH) and medial amygdaloid nucleus ( MeA) were analyzed. Results In OF, compared to CG group and SG group, LG group had significantly less time in center area, crossing number and total distance(P0.05 ). In EPM, compared to CG group and SG group, LG group had significantly less percentage of time, distance in open arms and total distance(P<0.001 ). Compared to CG group and SG group, LG group had significantly less ERa-IRs and ERβ-IRs in mPOA, VMH, and MeA(P<0.01). Conclusion Dams that are long-termly separated from their offspring may have anxiety-like behavior, and this behavior may be related to the significant reduction of ERa and ERβ in these brain regions.

ERα promotes transcription of tumor suppressor gene / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Apolipoprotein A-I (ApoA-I), the main protein component of high-density lipoprotein (HDL), plays a pivotal role in reverse cholesterol transport (RCT). Previous studies indicated a reduction of serum ApoA-I levels in various types of cancer, suggesting ApoA-I as a potential cancer biomarker. Herein, ectopically overexpressed ApoA-I in MDA-MB-231 breast cancer cells was observed to have antitumor effects, inhibiting cell proliferation and migration. Subsequent studies on the mechanism of expression regulation revealed that estradiol (E2)/estrogen receptor α (ERα) signaling activates

Effect of circulating estrogen level on the outcome of free fat grafting in nude mice / 中国修复重建外科杂志

Objective: To investigate the effect of circulating estrogen level on the outcome of free fat grafting in nude mice. Methods: Eighteen female nude mice aged 6-8 weeks (weighing, 20-25 g) were randomly divided into 3 groups ( n=6). The nude mice in the ovariectomized group were treated with ovariectomy. The nude mice in the high estrogen group and the normal estrogen group only made the same incision to enter the peritoneum without ovariectomy. The nude mice in the high estrogen group were given the estradiol (0.2 mg/g) every 3 days for 30 days. The other two groups were given the same amount of PBS every 3 days. At 30 days after operation, the tail vein blood of nude mice in 3 groups were detected by estradiol ELISA kit, and the free fat (0.3 mL) donated by the females was injected into the sub-scalp of nude mice. After 8 weeks of fat grafting, the samples were taken for gross observation and weighing, and the prepared slices were stained with HE staining, CD31-perilipin fluorescence staining, immunohistochemical staining of uncoupling protein 1 (UCP1), and immunofluorescence staining of estrogen receptor α. The diameter of adipocytes and vascular density of adipose tissue were measured. The mRNA expressions of UCP1 and estrogen receptor α were detected by realtime fluorescence quantitative PCR (qRT-PCR). Results: All nude mice survived during experiment. ELISA test showed that the concentration of estradiol significantly decreased in the ovariectomized group and increased in the high estrogen group compared with the normal estrogen group ( P<0.05). At 8 weeks after fat grafting, the graft volume from large to small was ovariectomized group, normal estrogen group, and high estrogen group. There was significant difference in wet weight between the ovariectomized group and high estrogen group ( P<0.05). Section staining showed that compared with the normal estrogen group, the adipocytes in the ovariectomized group were larger, the expression of peri-lipoprotein was weaker, the vascular density decreased, and the expressions of UCP1 was negative, and the estrogen receptor α positive cells reduced. The above observation results in the high estrogen group were contrary to those in the ovariectomized group. There were significant differences in the diameter of adipocytes, the vascular density of adipose tissue, the number of the estrogen receptor α positive cells between groups ( P<0.05). The results of qRT-PCR showed that the mRNA expressions of UCP1 and estrogen receptor α significantly increased in the high estrogen group and decreased in the ovariectomized group compared with the normal estrogen group, and the differences were significant ( P<0.05). Conclusion: The level of circulating estrogen has a significant effect on the outcome of free fat grafting in nude mice. Low estrogen level leads to hypertrophy of graft adipocytes, while high estrogen level leads to the production of a large amount of beige fat and high vascular density in fat grafts, which may be related to the activation of estrogen receptor α on adipocytes.

Low-magnitude vibration promotes osteogenesis of osteoblasts in ovariectomized osteoporotic rats via the estrogen receptor / 生物医学工程学杂志

The purpose of this study was to investigate the effect of low-magnitude vibration on osteogenesis of osteoblasts in ovariectomized rats with osteoporosis via estrogen receptor α(ERα). The mRNA expression of osteogenic markers were examined with qRT-PCR, based on which the optimal vibration parameter for promoting osteogenesis was determined (45 Hz × 0.9 g, g = 9.8 m/s

Pharmacodynamics and Mechanism of Chaijin Sanjie Prescription on Rats with Mammary Gland Hyperplasia / 中国实验方剂学杂志

Objective:To investigate the pharmacodynamics and mechanism of Chaijin Sanjie prescription (CJSJP) on rat mammary gland hyperplasia, in order to provide experimental basis for the research and development of new Chinese medicine. Method:SD rat model of mammary gland hyperplasia was established through exogenous intramuscular injection with estrogen and progesterone. After successful establishment of the model, the rats were randomly divided into normal group, model group, and low, medium and high-dose CJSJP groups (3.13, 6.26, 12.52 g·kg-1) and Rupixiao (0.517 g·kg-1) group, with 9 rats in each group. After 28 days of administration, estradiol (E2), progesterone (P) and rolactin (PRL) were measured by radioimmunoassay, uterus and ovary coefficients were calculated; nipple diameter and breast histopathology were observed, estrogen receptor-α(ER-α) expression in mammary gland was measured by immunohistochemistry, and gonadotropin-releasing hormone (GnRH) and gonadotropin-releasing hormone receptor (GnRH-R) mRNA expressions in hypothalamus, pituitary were measured by Real-time PCR. ICR mice were randomly divided into normal group, low, medium and high-dose CJSJP groups (5.2,10.4,20.8 g·kg-1) and Luotongding group (0.038 6 g·kg-1) according to their body weight. Twelve mice in each group were given drugs for 7 days, and 0.6% acetic acid was injected intraperitoneally for 30 minutes after the last administration. The writhing times were observed within 15 minutes. Result:Compared with the normal group, the diameter of nipple was widened, serum E2 was significantly increased (Pα expression were increased in model group. compared with model group, the diameter of nipple was significantly decreased in high dose group of CJSJP (P2 was decreased in all dose groups of CJSJP, pathological score of breast hyperplasia was decreased in middle and high dose groups of CJSJP, GnRH mRNA in hypothalamus was decreased in all dose groups of CJSJP. The writhing times of mice in high dose group of CJSJP was decreased (PConclusion:Chaijin Sanjie prescription can improve the lesions of breast hyperplasia. The therapeutic mechanism may be related to the regulation of GnRH gene expression in hypothalamus and the decrease of estrogen receptor expression.

Estrogenic Activity of Sanguiin H-6 through Activation of Estrogen Receptor α Coactivator-binding Site

A popular approach for the study of estrogen receptor α inhibition is to investigate the protein-protein interaction between the estrogen receptor (ER) and the coactivator surface. In our study, we investigated phytochemicals from Rubus coreanus that were able to disrupt ERα and coactivator interaction with an ERα antagonist. The E-screen assay and molecular docking analysis were performed to evaluate the effects of the estrogenic activity of R. coreanus extract and its constituents on the MCF-7 human breast cancer cell line. At 100 µg/mL, R. coreanus extract significantly stimulated cell proliferation (574.57 ± 8.56%). Sanguiin H6, which was isolated from R. coreanus, demonstrated the strongest affinity for the ERα coactivator-binding site in molecular docking analysis, with a binding energy of

Study on the regulatory mechanism of electroacupuncture based on thyroid pathway for mammary gland hyperplasia rats / 中国针灸

<p><b>OBJECTIVE</b>To study the regulating effect of thyroid pathway on electroacupuncture (EA) for mammary gland hyperplasia (MGH) so as to provide new research ideas for the mechanism of EA for MGH and to provide the evidence for clinical application.</p><p><b>METHODS</b>Sixty adult female SD rats were randomly divided into a blank group, a model group, an EA group, an EA with thyroidectomy group, an EA with sham operation group, 12 rats in each one. Except the blank group, the MGH model was established. Thyroid ablation was performed in the EA with thyroidectomy group, and sham operation was used in the EA with sham operation group, exposing thyroid without excision, 1 day after model establishment. EA was applied in the EA, the EA with thyroidectomy, and the EA with sham operation groups on the 4th day after model establishment, and not used in the other groups, but catching, routine disinfection and fixation were all the same as the above groups. The acupoints in the group A were bilateral "Tianzong" (SI 11), "Ganshu" (BL 18) and "Zusanli" (ST 36); and those in the group B were bilateral "Wuyi" (ST 15), "Hegu" (LI 4) and "Danzhong" (CV 17). The two groups of points were alternately used. EA, continuous wave, 2 Hz and 1 mA, was connected at "Tianzong" (SI 11) and "Ganshu" (BL 18), "Wuyi" (ST 15) and "Hegu" (LI 4) at the same side, 2 pairs EA a time, 20 min a time, once a day. All the intervention was given for 4 courses, 5 times as 1 course with 2 days between courses. After intervention, the height and diameter of the rat papilla were measured. Estrogen (E) and progestational hormone (P) in the serum were detected by enzyme linked immunosorbent assay (ELISA), and the contents and protein expression of estrogen receptor α (ERα) and progesterone receptor (PR) in the mammary glands were detected by immunofluorescence and Western-blot.</p><p><b>RESULTS</b>(1) The height and diameter of papilla in the model group increased compared with those in the blank group (both <0.01). The height and diameter of papilla in the EA, EA with sham operation groups reduced compared with those in the model group (all <0.01). Those in the EA with thyroidectomy group were lower than those in the model group, without statistical significance (both >0.05). (2) Compared with the blank group, E increased and P decreased in the model group (both <0.01). Compared with the model group, E decreased and P increased in the EA and EA with sham operation groups (all <0.01). The contents of E and P had no statistical significance between the model and the EA with thyroidectomy groups (both >0.05). (3) Compared with the blank group, the ERα content and protein expression increased and the PR content and protein expression decreased in the model group (all <0.01). Compared with the model group, the ERα content and protein expression decreased and the PR content and protein expression increased in the EA and EA with sham operation groups (all <0.01). The ERα and PR content and protein expression had no statistical significance between the model and the EA with thyroidectomy groups (all >0.05).</p><p><b>CONCLUSION</b>The effect of EA for MGH may be closely related to the regulation of thyroid.</p>

Electroacupuncture at intercostal nerve for mammary gland hyperplasia in rats / 中国针灸

<p><b>OBJECTIVE</b>To explore the correlation between efficacy of electroacupuncture (EA) on mammary gland hyperplasia (MGH) and the regulatory pathway of intercostal nerve.</p><p><b>METHODS</b>Fifty female SD rats were randomly divided into a blank group (group A, 12 rats), a model group (group B, 12 rats), an EA group (group C, 13 rats) and an intercostal nerve transection group (group D, 13 rats). The rats in the group B, group C and group D were prepared into MGH model; after model was successfully prepared, the 7th intercostal nerve was cut off in the group D. EA was applied at back acupoints including bilateral "Tianzong" (SI 11), "Ganshu" (BL 18) and "Shenshu" (BL 23) as well as chest acupoints including bilateral "Wuyi" (ST 15), "Hegu" (LI 4) and "Danzhong" (CV 17) in the group C and D. The two groups of acupoints were selected alternately. EA was given for 20 min, once a day; 5-day treatment was taken as one course; there was an interval of 2 days between course; totally 20 treatments were given. After treatment, the height and diameter of papilla were observed; the contents of serum estradiol (E) and progestin (P), the expression of estrogen receptor α (ERα) and progestrone receptor (PR) in mammary gland were measured.</p><p><b>RESULTS</b>(1) The height and diameter of papilla: after treatment, the height and diameter of papilla in the group C were significantly smaller than those in the group B (both<0.05); the height and diameter of left-side papilla in the group D were significantly bigger than those in the group C (both<0.05). (2) Serum Eand P: after treatment, compared with the group B, the contents of Eand E/P were reduced and the content of P was increased in the group C and group D (all<0.05). Compared with the group C, the contents of Eand E/P were increased and the content of P was reduced in the group D (all<0.05). (3) ERα and PR in mammary gland: compared with the group B, the content of ERαwas decreased and the content of PR was increased in the group C (both<0.05). Compared with the group C, the content of ERαwas increased and the content of PR was decreased in the group D ((both<0.05).</p><p><b>CONCLUSION</b>The efficacy mechanism of EA for MGH is likely to be related with the pathway of intercostal nerve; the mechanism may be acupuncture regulating the contents of serum Eand P as well as contents of ERα and PR in mammary gland.</p>

High-affinity Binding Sites for Estrogen Receptor α in the p21WAF1/CIP1 Promoter Region in Breast Cancer MCF-7 Cells / 中国医科大学学报

Objective To investigate the specific sites that estrogen receptor (ER)α could be recruited to in the p21WAF1/CIP1 promoter region to regulate its transcriptional activity in MCF-7 cells,and to clarify the molecular mechanism of suberoylanilide hydroxamic acid (SAHA) and leptin in the regulation of p21WAFI/CIP1 promoter function.Methods MCF-7 cells were starved by culturing them in fetal calf serum-free medium for 24 hours,and then treated with 20 μmol/L of 0.88 μL SAHA (SAHA group) or 0.625 nmol/L of 10 μL leptin (leptin group) for 24 hours,or cultured in complete RPMI-1640 medium (control group).Cell lysates were incubated with anti-ERα antibody for ChIP analysis.The relative expression levels of DNA fragments,ranging from the TSS to upstream of the p21WAF1/CIP1 promoter region (+2 to-4 000 bp),that bound the antibody were detected by real-time PCR.Results In the control group,the relative expression levels of f1,f2,and f8 DNA fragments that bound the antiERα antibody were two-fold higher than the relative expression of the f9 fragment (P ＜ 0.01).In the SAHA and leptin groups,the relative expression of f1 to f10 DNA fragment that bound anti-ERα antibody was significantly lower than that of the control.The binding affinity of ERα for the f8 fragment was the lowest (P ＜ 0.01) in the SAHA group,and it was significantly lower than that in the leptin group (P ＜ 0.01).Conclusion ERα could be recruited to the p21WAFI/CIP1 promoter via signaling pathways activated during the proliferation of breast cancer MCF-7 cells.Moreover,the DNA fragment ranging from-2 800 to-3 200 bp upstream of the p21 WAF1/CIP1 promoter is the target functional region for high-affinity binding with ERα.

Effect of Danggui Shaoyao Powder on the Uterine Structure and Estrogen Receptor Expression in Model Rats in Perimenopausal Period / 中国药房

OBJECTIVE:To investigate the effect of Danggui shaoyao powder (DSS) on uterine structure and expressions of estrogen receptorα(ERα),estrogen receptorβ(ERβ)in uterine cavity epithelium and matrix in model rats in perimenopausal peri-od. METHODS:40 female SD rats were randomly divided into sham operation group (normal saline),model group (normal sa-line),DSS low-dose,medium-dose,high-dose groups(1.94,3.87,7.44 g/kg),8 in each group. Except that rats in sham opera-tion group received resection of fat nearby ovaries,rats in other groups received resection of bilateral ovaries to induce models in perimenopausal period. After modeling,rats were intragastrically administrated once a day,for 8 weeks. After administration,wet mass of uterine was weighted. Changes in uterine morphology and structure of rats were observed,expressions levels of ERα and ERβ in uterine cavity epithelium and matrix were determined. RESULTS:Compared with sham operation group,rats in model group showed low columnar in endometrial columnar epithelium,lamina propria layer,muscular layer and serous layer were signifi-cantly atrophied,stromal cells had obvious nuclear condensation. There was marked decrease in uterine wet mass,uterine cavity ar-ea and endometrial thickness as well as the number of uterine glands(P<0.01),and the expression levels of ERαand ERβin uter-ine cavity epithelium and matrix were significantly reduced(P<0.01). Compared with model group,the atrophy degree of endome-trium and lamina propria layer had no significant differences in DSS each dose groups. However,lamina propria layer was rich in glands,and there were significant differences in uterine wet mass,uterine cavity area,endometrial thickness,ERα expression level in uterine cavity epithelium and matrix (P>0.05). However, the number of uterine glands in DSS medium-dose,high-dose groups was significantly increased(P<0.01),and ERβexpres-sion level in uterine cavity epithelium and matrix in DSS high-dose group was significantly increased (P<0.05 or P<0.01). CONCLUSIONS:DSS has not obvious effect on im-proving the symptoms of uterine gland atrophy of model rats in perimenopausal period,but it can increase the number ofuterine glands,and the mechanism may be associated with improving the ERβ expression level in uterine cavity epithelium and ma-trix.

Gene polymorphisms of estrogen receptor α correlated with hypospadias in children / 中华男科学杂志

Objective@#To investigate the association of the polymorphisms of the gene of estrogen receptor α 1 (ESR1) with the risk of hypospadias in children of Northeast China.@*METHODS@#This study included 95 hypospadias patients aged 3.2±0.6 years and 105 children aged 3.1±0.7 years as normal controls. Using PCR and gene sequencing, we determined the genotypes of the polymorphisms of ESR1 rs2077647 and rs6932902 in the two groups of subjects.@*RESULTS@#The results of PCR and gene sequencing showed statistically significant differences in the genotype and allele frequency distribution of the polymorphisms rs2077647 (χ2 = 8.552) and rs6932902 (χ2 = 16.251) (P<0.05) in the hypospadias and control groups. The hypospadias patients, in comparison with the normal controls, exhibited a markedly higher frequency of the SNP C allele in rs2077647 (OR = 1.410 ［1.130－1.759］, P<0.05), but a remarkably lower frequency of the SNP G allele in rs6932902 (OR = 2.263 ［1.503－3.408］, P<0.01).@*CONCLUSIONS@#The rs2077647 and rs6932902 polymorphisms of the ESR1 gene are associated with the risk of hypospadias, and so is its haplotype in children in Northeast China.

Estrogen aggravates inflammatory bowel disease in rats through estrogen receptor alpha / 第二军医大学学报

Objective To explore the specific mechanism by which estrogen affects the inflammatory bowel disease (IBD) in rats. Methods The model of IBD in rats was established with 30% of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) ethanol solution through the rectocolon. The body weight, disease activity index(DAI) score, colorectal length, myeloperoxidase (MPO) concentration, and H-E staining were used to verify the successful IBD model. The IBD rats were separately treated with saline(500 μL), estrogen(1 mg/kg,in 500 μL normal saline), and PPT, a specific agonist of estrogen receptor alpha (ERα; 3 mg/kg, in 500 μL normal saline), or estrogen(1 mg/kg,in 500 μL normal saline) + ERα specific antagonist MPP(3 mg/kg, in 500 μL normal saline). And the inflammation status was observed. Results The model of IBD in rats was successfully induced by TNBS. Compared with the normal saline group, rats in TNBS group had significantly reduced body weight and increased DAI scores, with MPO value increased and with notable inflammatory response of the rectocolon. Compared with normal saline group, estrogen or PPT significantly aggravated the inflammation response. Estrogen treatment significantly reduced the body weight of IBD rats, increased DAI scores, and aggravated the inflammatory response, with the colorectal length reduced; PPT reduced the colorectal length. MPP treatment reversed the effect of estrogen. Compared with the estrogen group, MPP+estrogen treatment significantly increased the body weight and reduced the DAI scores, with colorectal length increased. Conclusion Estrogen can promote the development and progression of TNBS-induced IBD, which might be mediated through ERα.

Differential expression of estrogen receptor α and progesterone receptor in the normal and cryptorchid testis of a dog / 한국실험동물학회지

Descending of the testes is an important process for spermatogenesis and cryptorchidism is one of the most relevant genital defects in dogs. In a previous study, we observed abnormal morphology and proliferation of Sertoli cells in a cryptorchid testis. In the present study, we investigated the expression of estrogen and progesterone receptors in the normal and cryptorchid testis of a dog. Elective orchidectomy was performed on the dog's abdominal right testis (undescended, cryptorchid) and scrotal left testis (descended, normal). In the normal testis, estrogen receptor α immunoreactivity was detected in Leydig cells alone, while estrogen receptor α immunoreactivity in the cryptorchid testis was significantly prominent in the Sertoli cells as well. In addition, progesterone receptor immunoreactivity in the control testis was detected in the spermatids, but was not detected in the cryptorchid testis. This result suggests that unilateral cryptorchidism causes increases of estrogen receptor α expression in Sertoli cells.

RASSF1A and RASSF1A methylation′s relationship with breast cancer / 实用肿瘤学杂志

Breast cancer is one of the most common malignant tumors in women.Early diagnosis plays a very important role in the treatment of breast cancer.Recently,with the development of epigenetics,it gives us a new orientation for early detection for cancers.The most understood mechanism of epigenetics is DNA methyla-tion.Ras associated domain family 1A gene(RASSFlA)promoter methylation occurres in tumor′s early stage,and have a statistically concern with tumor′s TNM stage,invasiveness and outcomes.Moreover,DNA methylation can be reversed,so RASSF1A can be a promising candidate for early breast cancer detection biomarker,and can be a potential orientation for breast cancer treatment.

Estrogenic activities of four components from pregnant mare’s urine extract / 中国药理学通报

Aim To investigate the estrogenic activities of four components from pregnant mare’s urine extract. Methods The estrogenic activities of four components were assessed using two in vitro tests:the MCF-7 cell proliferation assay (E-screen test)and the luciferase transfected CHO cell gene reporter assay.In the lucifer-ase reporter gene assay,the reporter gene plasmids PGM-ERE-Luc and ERαor ERβand a control plasmid (pRL-cmv)were transiently co-transfected into CHO cells to establish an ERα-or ERβ-cell screening system which was used to measure estrogenic activity of four compounds.Results MCF-7 cells treated with HP, DHP,PT and HA significantly proliferated,thereby of-fering in vitro evidence for the estrogenic activities of HP,DHP,PT and HA,and they showed dose-depend-ent activities.Compared EC50 of PE and RPE with that of E2 ,HP,DHP,PT and HA exerted relatively weak estrogenic activities.The in vitro ER-mediated reporter gene assay revealed that HP,DHP,PT and HA dis-played estrogenic activities mediated by ERβor ERα. Compared with the EC50 of E2 ,HP,DHP,PT and HA exhibited lower estrogenic potencies.Conclusion HP, DHP,PT and HA possess weaker estrogenic activities than E2 .

A meta-analysis of ESRαrs2234693 polymorphism associated with pros-tate cancer risk / 中国病理生理杂志

AIM:To investigate the pooled association between estrogen receptor α( ESRα) rs2234693 poly-morphism and prostate cancer risk .METHODS:A systematic literature search was performed to identify the related stud-ies (up to April 2014) in several online databases including PubMed , the CNKI and Wanfang online libraries .Odds ratios with 95%confidence intervals were used to calculate the strength of association in the random effect model .RESULTS:A total of 20 studies including 4 623 cases and 9 850 controls were enrolled in the final meta-analysis.The results indicated that ESRαrs2234693 polymorphism was significantly associated with prostate cancer risk (P0.05 ) .CONCLUSION:This meta-analysis suggests that ESRαrs2234693 polymorphism is significantly associated with prostate cancer risk , espe-cially in Caucasians .

Recognition of environmental estrogen-like compounds based on fluorescent imaging analysis of ERα-EGFP nuclear granules formation / 军事医学

Objective To establish a quick method to probe the environmental estrogen-like compounds via fluorescent imaging analysis in high content analysis (HCA) technology.Methods HCA assays were performed to quantitatively in-vestigate the effect of collected environmental pollutants , including bisphenol A , nonylphenol , 1,2-phenylenediamine , 4-aminophenol, resorcinol, 3-aminophenol, 1,4-phenylenediamine and 2,5-diaminotoluene on nuclear granules formation ( Foci-formation) of estrogen receptor α( ERα)-EGFR( enhanced green fluorescent protein ) fusion-protein, which was se-lected as a research model in this study .The results were confirmed by the ERαtranscriptional activity by luciferase as-says.Results Compounds 1,2-phenylenediamine, 4-aminophenol, resorcinol, 3-aminophenol, 1,4-phenylenediamine and 2,5-diaminotoluene sulfate could not induce the ERα-EGFR nuclear granule formation.17-β-Estradiol, bisphenol A, or nonylphenol enhanced ERα-EGFR nuclear granule formation in a dose-dependent manner .The EC50 value was (4.17 ± 0.41) nmol/L, (1.48 ±1.79) μmol/L,or (3.70 ±0.78) μmol/L, respectively.The minimum detectable concentration was 1 nmol/L (17-β-estradiol)and 300 nmol/L (bisphenol A, nonylphenol).In luciferase tests, 17-β-estradiol, bisphe-nol A, or nonylphenol increased ERαtranscriptional activity in a dose-dependent manner ,and the EC50 value was (4.46 ±0.56) nmol/L, (2.31 ±0.21) μmol/L, or (6.60 ±0.94) μmol/L, respectively.The minimum detectable concentration was 3 nmol/L (17-β-estradiol), 300 nmol/L (bisphenol A),and 1 μmol/L (nonylphenol).Conclusion As an efficient method for ERαagonist identification , HCA assays based on the cell image phenotypes analysis can be used in quick recog -nition of environmental compounds with ER agonist-like activity.In all experimental compounds , only bisphenol A and non-ylphenol have a clear ER agonist-like activity .

Epigenetic regulation of estrogen receptor-αin breast cancer / 实用肿瘤学杂志

Recently,in the management of estrogen receptor(ER)positive breast canner,endocrine thera-py is the main treatment method;and estrogen receptor -α( ER-α) has obtained popularity as one of the most common targets .There are many known risk factors for ER function in breast canner such as ER gene mutation ;unbalanced microenvironment;signal transduction pathway disorders .While more and more attention is paid to the changes in ER expression and function induced by epigenetic aberrations .ER gene promoter methylation induces down regulation and deletion in ER expression ,which has not only a most highly incidence in epigenetic aberra-tions,but also a widen degree of research .Histone modification could influence ER -αexpression and function , either.However,the special mirco RNAs(miRNAs)are also implicated in the regulation of ER -α,and affect the therapy of tamoxifen in breast tumor .